Description of Clinical Expertise

I am a Board Certified Adult Neurologist who has been in active and continuous practice since 1987. I have facility in the treatment of a broad range of Neurological Disorders. I have special expertise in the diagnosis and management of ALS patients.

Description of Research Expertise

Research in my lab focuses on two topics: 1) activity-dependent development of circuits in the central nervous system and 2) healthful compensatory responses of cells and organisms to stressful conditions. We use genetically manipulated mice, primary neuron tissue culture and C.elegans in our studies; our approach is cell and molecular biology.
During development synaptic activity refines and patterns connections among neurons and this is required for precise high-level behavior. We have found that glutamatergic synapses that include the GluA1 subunit have a privileged role in this process likely a function of specific electrophysiological properties and through the assembly of a large multi-protein complex in the sub-synaptic domain. A critical molecular component of this complex is SAP97, a scaffolding protein with >90 known binding partners. We have taken a variety of approaches to identifying the critical binding partners of SAP97 that transduce activity of glutamate receptors assembled with GluA1 into dendrite growth, synapse specification and circuit function. Insight in the molecular logic of SAP97 function will have implications for childhood maladies such as intellectual disability and autism/autism-spectrum disorders.
Mutations in protein such as Cu++/Zn++ SOD and TDP43 cause adult onset neurodegenerative diseases such as Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. We have found that these mutant proteins evoke maladaptive changes in cellular and organismal intermediary metabolism – re-wiring metabolism can blunt the adverse effects on neuronal survival. We have made parallel observations in an infantile/childhood motor neuron disease called Spinomuscular atrophy. In addition, mutant protein misfolding can be injurious to neurons by disrupting cellular protein homeostasis and we have identified suppressors of this toxicity. Targeting proximal events in neurodegenerative diseases will lead to novel therapeutic approaches.